Summary of Safety and Effectiveness Data
`
`TAXUSTM Express2 TM Coronary Stent System (P030025)
`
`SUMMARY OF SAFETY AND EFFECTIVENESS DATA
`
`
`I.
`
`GENERAL INFORMATION
`
`
`Product Generic Name:
`
`Drug-Eluting Coronary Stent System (NIQ)
`
`Product Trade Name:
`
`TAXUS™ Express2TM Paclitaxei-Eiuting
`Coronary Stent System (Monorail and Over­
`the-Wire)
`
`Applicant's Name and Address: Boston Scientific Corporation
`One Boston Scientific Place
`Natick, MA 01760
`
`Premarket Approval Application (PMA) Number: P030025
`
`Date of Panel Recommendation:
`
`November 20, 2003
`
`Date of Notice of Approval to Applicant:
`
`March 4, 2004
`
`II.
`
`INDICATIONS FOR USE
`
`The TAXUSTM Express2 TM Paclitaxei-Eiuting Coronary Stent System is indicated
`for improving luminal diameter for the treatment of de novo lesions_::: 28mm in
`length in native coronary arteries::: 2.5 to_::: 3.75 mm in diameter.
`
`Ill.
`
`CONTRAINDICATIONS
`
`Use of the TAXUSTM Express2 TM Paclitaxei-Eiuting Coronary Stent System is
`contraindicated in patients with:
`• Known hypersensitivity to paclitaxel or structurally-related compounds.
`• Known hypersensitivity to the polymer or its individual components (see
`details in Section V- Product Description, below)
`
`Coronary Artery Stenting is contraindicated for use in:
`• Patients in whom anti-platelet and/or anticoagulant therapy is
`contraindicated.
`• Patients judged to have a lesion that prevents complete inflation of an
`angioplasty balloon or proper placement of the stent or delivery device.
`
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`

`Summary of Safety and Effectiveness Data
`
`TAXUSTM Express2 TM Coronary Stent System (P030025)
`
`IV.
`
`WARNINGS AND PRECAUTIONS
`
`The warnings and precautions can be found in the TAXUS Express2 Paclitaxei­
`Eiuting Coronary Stent System labeling.
`
`V.
`
`PRODUCT DESCRIPTION
`
`The TAXUS Express2 Stent System is a device I drug combination product
`comprised of two regulated components: a device (Express2 Coronary Stent
`System) and a drug component (a formulation of paclitaxel contained in a
`polymer coating). The characteristics of the T AXUS Express2 Stent System are
`described in Table 1.
`Tabl 1. TAXUS E
`s
`'f
`tent ;ystem p
`e
`rod
`uct D
`escr1p11on
`xpress
`T AXUS Express'
`T AXUS Express'
`Monorail (MR) Stent Delivery System
`Over-The-Wire (OTW) Stent Delivery System
`
`8, 12, 16, 20, 24, 28, 32
`
`8, 12, 16,20,24,28,32
`
`2.50, 2.75, 3.00, 3.50
`
`2.50, 2. 75, 3.00, 3.50
`
`A 316L surgical grade stainless steel Express stent
`A conformal coating of a polymer carrier loaded with 1 ).lQ/mm;(. paclitaxel in a slow release
`(SR)* formulation applied to the stent with a maximum nominal drug content of 209 ll9 on the
`laroest stent (3.50x32mm).
`
`140 em
`
`135 em
`
`Y-Connector (Side arm for access to balloon
`Single access port to inflation lumen.
`inflation/deflation lumen. Straight arm is
`Guidewire exit port is located
`continuous with shaft inner lumen). Designed
`approximately 25 em from tip. Designed
`for guidewire < 0.014".
`for guidewire < 0.014".
`A compliant balloon, nominally 0.3 mm longer than the stent, with two radiopaque markers.
`
`Nominal inflation Pressure: 9 ATM; Rated Burst Inflation Pressure: 18 ATM
`
`": 0.058"
`
`?,0.066"
`
`Available Stent
`Lengths (mm)
`Available Stent
`Diameters (mm)
`
`Stent Material
`Drug Component
`
`Delivery System
`Working Length
`Delivery System
`Y -Adapter Ports
`
`Stent Delivery
`Balloon
`Balloon Inflation
`Pressure
`Guide Catheter
`Inner Diameter
`Catheter Shaft
`Outer Diameter
`
`1.8F proximally, 2.7F distally (0 up to
`3.0mm, and 8-20 mm long stents with 0 >
`3.0mm)
`2.0F proximally, 2.7F distally (24-32mm
`lana stents with 0 > 3.0mm)
`• release rate IS a funct1on of we1ghUwe1ght rat1o of polymer and drug, and (SR) IS the formulation that
`was studied clinically and is used in the marketed product
`
`3.2F proximally, 2.7F distally
`
`A. Device Component Description
`
`The device component consists of the Express rM stent pre-mounted onto a
`stent delivery system (SDS); either the Express2
`TM Over-the-Wire (OTW)
`delivery system, or the Express2
`TM Monorail (MR) delivery system. The
`Express2 OTW and MR delivery systems were previously approved for
`
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`

`

`Summary of Safety and Effectiveness Data
`
`TAXUSTM Express2TM Coronary Stent System (P030025)
`
`deployment of the uncoated Express stent
`September 11, 2002).
`
`in P020009
`
`(approved
`
`The 2.5-3.5mm diameter 316L stainless steel stents use one design. The
`same stent is crimped on various size delivery catheter balloons, which are
`sized from 2.5 to 3.5mm. Because the identical stent component is used for
`the entire 2.5-3.5mm diameter range, the total drug per stent is a function of
`stent length, irrespective of stent diameter.
`
`The Express2 Delivery Catheters were not used in the pivotal clinical trial
`(TAXUS IV). The TAXUS IV trial used the Express Delive7 Catheters.
`The only differences between the Express and the Express versions of
`the delivery catheters are that: (1) the Express2 catheter changed one of
`the shaft materials to another material that was used in other components
`of the original Express delivery catheter shaft; and (2) the Express2
`manifold was molded slightly differently to allow better retention in the
`packaging. This PMA requested approval of only the Express2 OTW and
`MR delivery systems for use in delivering the TAXUS Express stent.
`Appropriate pre-clinical testing was provided to support the Express2 stent
`delivery system, and acute (30 day) safety and performance data was
`submitted March 1, 2004 (TAX US V trial, 1167 patients) to support the
`clinical safety of the TAXUS Express stent mounted on the Express2
`catheter design.
`
`B. Drug Component Description
`
`The drug component of the TAXUS Express2 Paclitaxel-eluting Coronary
`Stent System (referred to as the TAXUS Express Stent) consists of
`paclitaxel (the active ingredient) and Translute™ polymer carrier (the
`inactive ingredient).
`
`B1. Paclitaxel
`
`The active pharmaceutical ingredient in the TAXUS Express Stent is
`paclitaxel. It is a white powder, isolated from a spectrum of Taxus
`species and hybrids. The Chemical name of paclitaxel is:
`Benzenepropanoic acid, 13-(benzoylamino)-a-hydroxy-,6, 12b­
`bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9, 10,11, 12,12a, 12b­
`dodecahydro-4, 11-dihydroxy-4a,B, 13,13-tetramethyl-5-oxo-7, 11­
`methano-1 H-cyclodeca[3,4]benz[1 ,2-b]oxet-9-yl ester, [2aR­
`[2aa,413,4a13,613,9a (aR*, 13S*), 11a, 12a, 12aa, 12ba]]-.
`
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`

`Summary of Safety and Effectiveness Data
`
`TAXUSTM Express2 TM Coronary Stent System (P030025)
`
`The chemical structure of paclitaxel is shown below.
`
`Figure 1. The Chemical Structure of Paclitaxel
`
`0cf: i
`
`!
`OH
`
`Paclitaxel is a diterpenoid with a characteristic taxane skeleton of 20
`carbon atoms, a molecular weight of 853.91 g/mol and a molecular
`formula of C47H51 N014. It is highly lipophilic, insoluble in water,
`but freely soluble in methanol, ethanol, chloroform, ethyl acetate and
`dimethyl sulfoxide.
`
`82. Inactive Ingredients
`
`The only inactive ingredient in the TAXUS Express stent is SIBS
`[poly(styrene-b-isobutylene-b-styrene)], a tri-block copolymer (trade
`name: Translute TM), that is composed of styrene and isobutylene units
`built on 1 ,3-di(2-methoxy-2-propyl)-5-tert-butylbenzene. It is an
`hydrophobic elastomeric copolymer with a molecular weight (Mn­
`number average molecular weight) of 80,000 to 130,000 g/mol and a
`polydispersity index of 1.0 to 2.0. The polymer is mixed with the drug
`paclitaxel and then applied to the stents. There is no primer or topcoat
`layer. The drug/polymer coating is adhered to the entire surface (i.e.,
`luminal and abluminal) of the stent. The structural formula for the
`polymer is shown below.
`
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`

`

`Summary of Safety and Effectiveness Data
`
`
`
`TAXUSTM Express2 TM Coronary Stent System (P030025)
`
`Figure 2. The Chemical Structure of SIBS [poly(styrene-b-isobutylene-b­
`styrene)]
`
`m "' repeating units of styrene
`n "' repeating units or isobutylene
`
`Product Matrix and Paclitaxel Content
`
`TM Stent System Product Matrix and Paclitaxel
`
`Table 2. TAXUSTM Express2
`Content
`Product Code MR Product Code OTW Nominal Expanded
`Stant Inner Diameter
`(mm)
`
`H7493897008250
`H7493897008270
`H7493897008300
`H7493897008350
`H7493897012250
`H7493897012270
`H7493897012300
`H7493897012350
`H7493897016250
`H7493897016270
`H7493897016300
`H7493897016350
`H7493897020250
`H7493897020270
`H7493897020300
`H7493897020350
`H7493897024250
`H7493897024270
`H7493897024300
`H7493897024350
`H7493897028270
`H7493897028300
`H7493897028350
`H7493897032270
`H7493897032300
`H7493897032350
`
`H7493896808250
`H7493896808270
`H7493896808300
`H7493896808350
`H7493896812250
`H7493896812270
`H7493896812300
`H7493896812350
`H7493896816250
`H7493896816270
`H7493896816300
`H7493896816350
`H7493896820250
`H7493896820270
`H7493896820300
`H7493896820350
`H7493896824250
`H7493896824270
`H7493896824300
`H7493896824350
`H7493896828270
`H7493896828300
`H7493896828350
`H7493896832270
`H7493896832300
`H7493896832350
`
`2.50
`2.75
`3.00
`3.50
`2.50
`2.75
`3.00
`3.50
`2.50
`2.75
`3.00
`3.50
`2.50
`2.75
`3.00
`3.50
`2.50
`2.75
`3.00
`3.50
`2.75
`3.00
`3.50
`2.75
`3.00
`3.50
`
`Nominal
`Un-expanded Stent
`Length (mm)
`
`8
`8
`8
`8
`12
`12
`12
`12
`16
`16
`16
`16
`20
`20
`20
`20
`24
`24
`24
`24
`28
`28
`28
`32
`32
`32
`
`Nominal
`Paclitaxel Content
`(~g)
`50
`50
`50
`50
`79
`79
`79
`79
`108
`108
`108
`108
`137
`137
`137
`137
`151
`151
`151
`151
`180
`180
`180
`209
`209
`209
`
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`

`Summary of Safety and Effectiveness Data
`
`TAXUSTM Express2TM Coronary Stent System (P030025)
`
`C. Mechanism of Action
`
`The mechanism (or mechanisms) by which a TAXUS Express Stent affects
`neointimal production as seen in clinical studies has not been established.
`Paclitaxel promotes the assembly of microtubules from tubulin dimers and
`stabilizes microtubules by preventing depolymerization. This stability results
`in the inhibition of the normal dynamic reorganization of the microtubule
`network that is essential for vital interphase and mitotic cellular functions.
`
`VI.
`
`ALTERNATIVE PRACTICES OR PROCEDURES
`
`Treatment of patients with coronary artery disease may include exercise, diet,
`drug therapy, percutaneous coronary interventions (such as angioplasty, bare
`metal stents, coated stents, and other drug eluting stents), and coronary artery
`bypass surgery (CABG).
`
`VII.
`
`MARKETING HISTORY
`
`The TAXUS Express2 Paclitaxei-Eiuting Coronary Stent System is
`commercially available in the following countries:
`
`• Argentina
`• Austria
`• Belgium
`• Brazil
`• Chile
`• China
`• Columbia
`• Czech Rep.
`• Denmark
`• Egypt
`
`• Finland
`• France
`• Germany
`• Greece
`• Hong Kong
`• Hungary
`•
`Iceland
`•
`India
`• Ireland
`•
`Italy
`
`• Jordan
`• Liechtenstein
`• Luxemburg
`• Malaysia
`• Mexico
`• Netherlands
`• Norway
`• New Zealand
`• Philippines
`• Poland
`
`• Portugal
`• Singapore
`• South Africa
`• Spain
`• Sweden
`• Switzerland
`• Thailand
`• United Kingdom
`• Uruguay
`
`As of June 1, 2003, approximately 13,000 T AXUS Express Stents have been
`distributed outside of the U.S. No products have been withdrawn from the
`market in any country for any reason.
`
`VIII.
`
`SUMMARY OF NON-CLINICAL STUDIES
`
`A series of non-clinical laboratory studies were performed -those related to the
`stent and the stent delivery system [i.e., the stent mounted on either the
`Monorail (MR) or Over-the-Wire (OTW) stent delivery system (SDS)], the
`polymer substance [i.e., polyisobutylene styrene (SIBS)], the drug substance
`
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`

`Summary of Safety and Effectiveness Data
`
`TAXUSTM Express2 TM Coronary Stent System (P030025)
`
`(i.e., paclitaxel), and the finished combination product (i.e., TAXUS Express2
`paclitaxel-eluting coronary stent).
`
`A. Biocompatibility Studies
`
`A series of GLP and non-GLP biocompatibility tests and USP
`Physicochemical tests were conducted to demonstrate the components of
`the TAXUS Express2 Paclitaxei-Eiuting Coronary Stent System (Monorail
`and Over-the-Wire) are non-toxic. Tests were conducted on ethylene
`oxide-sterilized bare metal stents, stent delivery systems, polymer films,
`and polymer-only coated stainless steel (SS) coupons. These test articles
`were processed in the same manner as the finished TAXUS Express2
`product, except that where polymers were present (i.e., films and
`coupons), the drug substance, paclitaxel, was not included in the polymer
`coating. With the exception of the inclusion of the drug substance, the
`surface treatment, coating processing, amount of coating per unit area,
`and sterilization processes were equivalent for both the stents and
`coupons utilized during this testing. In all of these test systems, the
`materials were non-reactive and produced no greater response than the
`negative control employed in each test system.
`
`All biocompatibility testing was conducted in accordance with:
`
`• Guidance for the Submission of Research and Marketing Applications
`for lnterventional Cardiology Devices; published by the lnterventional
`Cardiology Devices Branch, Division of Cardiovascular, Respiratory
`and Neurology Devices, Office of Device Evaluation in May 1995.
`
`•
`
`ISO 10993-1, Biological Evaluation of Medical Devices: Evaluation
`and Testing.
`
`The GLP and non-GLP biocompatibility studies are summarized in Table
`3.
`
`Table 3. Biocompatibility Test Summarv
`. Stent and delivery systems: Pass (non-cytotoxic)
`Test Name
`Test Description
`Test Article and Results
`Cytotoxicity
`ISO 10993-5: In Vitro
`Cytotoxicity (L929 MEM
`Elution)
`ISO 10993-10: Sensitization
`(Kligman Maximization)
`
`Sensitization
`
`• Polymer-only coated 316l SS coupon: Pass (non­
`cvtotoxicl
`• Stent and delivery systems: Pass (non-sensitizing)
`• Polymer-only coated 316L SS coupon: Pass (non­
`sensitizinal .
`• Stent and delivery systems: Pass (non-irritant)
`• Polymer-only coated 316L SS coupon: Pass (non­
`irritantl
`• Stent and delivery systems: Pass (non-toxic)
`• Polymer-only coated 316L SS coupon: Pass (non­
`toxi~l
`
`Intracutaneous
`Reactivity
`
`ISO 10993-10: Irritation
`(Injection)
`
`Acute Systemic
`Toxicity
`
`ISO 1 0993-11: Systemic
`Toxicity (Acute)
`
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`Summary of Safety and Effectiveness Data
`
`TAXUSTM Express2 TM Coronary Stent System (P030025)
`
`Test Name
`Pyrogenicity
`
`Hemocompatibility
`
`Implantation
`
`Genotoxicity
`
`Test Description
`LAL
`ISO 10993-11: Systemic
`Toxicity (Material-Mediated
`Rabbit)
`Direct Contact Hemolysis
`
`Lee and White Coagulation
`
`14-Days (Rabbit,
`Intramuscular)
`30-Days (Rabbit,
`Intramuscular}.
`14-Day Repeat Dose
`Subchronic Toxicity (Mouse,
`Intravenous)
`90-Day Chronic Toxicity
`(Mouse, lntraceritoneal)
`Bacterial Reverse Mutation
`Assay (Ames Test)
`In Vitro Chromosomal
`Aberration (human blood
`lvmohocvtes)
`In Vivo Mouse Micronucleus
`Test
`
`Test Article and Results
`• Stent and delivery systems: Pass (non-pyrogenic)
`
`pyrogenic)
`
`. Polymer-only coated 316L SS coupon: Pass (non­
`. Stent and delivery systems: Pass (non-hemolytic)
`
`• Polymer-only coated 316L SS coupon: Pass (non­
`hemolvtic)
`• Stent and delivery systems: Pass (no change in
`coagulation time)­
`
`. Stent and delivery systems: Pass (non-toxic)
`
`• Stent and delivery systems: Pass (non-toxic)
`
`• Stent and delivery systems: Pass (non-toxic)
`
`• Polymer-only cast film: Pass (non-toxic)
`
`• Polymer-only coated 316L SS coupon: Pass (non­
`mutagenic)
`
`. Polymer-only cast film: Pass (non-clastogenic)
`. Polymer-only cast film: Pass (non-mutagenic)
`USP Physicochemical Extracts . Stent and delivery systems: Pass
`
`.
`
`Volatile/Metal
`Extracts
`. .
`Note. Express BMS & DES blocompat1b11ity studtes were conducted 1n accordance wtth GLPs. A rattonale
`was provided for the non-GLP biocompatibility studies of Polymer-only coated SS/coupon and Polymer-only
`film studies to demonstrate that appropriate animal care procedures were followed, and data integrity was
`maintained.
`
`Since the sponsor did not conduct the traditional battery of IS0-10993
`testing on the finished TAXUS Express Stent (i.e., containing the drug
`substance), sub-chronic toxicity, thrombogenicity, and implantation of the
`final TAXUS Express product, containing all components and processing,
`were evaluated in porcine, rabbit, and canine models of stent-mediated
`vascular injury. The significant animal studies are summarized separately
`in Section VIII F- Animal Studies (below).
`
`The genotoxicity, carcinogenicity, and reproductive toxicity of TAX US
`Express Stents have not been evaluated. However, the genotoxicity,
`carcinogenicity, and reproductive toxicity of paclitaxel have been
`investigated in bacterial and mammalian cells in vitro and in laboratory
`animals in vivo.
`
`Boston Scientific provided a letter from the drug substance manufacturer,
`lndena S.p.A., authorizing access to a Drug Master File (DMF) in support
`of this application. lndena manufactures a generic form of the drug
`Taxol®, a Bristol-Myers Squibb drug product that is approved for injection
`for multiple oncologic indications. In vivo animal and in vitro
`pharmacology and toxicology studies as well as in vivo and human
`pharmacokinetic studies were conducted on Taxol® to provide information
`
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`

`Summary of Safety and Effectiveness Data
`
`TAXUSTM Express2 TM Coronary Stent System (P030025)
`
`about systemic, regional and local toxicity, dose-related toxicity,
`distribution profiles, end-organ disposition, drug metabolism and potential
`drug-drug interactions.
`
`There is no evidence to suggest that any chemical interactions occur,
`which would form a new intermediate or molecular entity, between
`paclitaxel or the polymeric carrier used in the TAXUS Express Stents.
`
`Formal carcinogenicity testing on the final TAXUS Express Stent was not
`conducted. Because some paclitaxel remains on the product, and the
`carcinogenic potential of the SIBS polymer coating had not previously
`been investigated, an appropriate rationale was provided to demonstrate
`that the carcinogenic potential of the T AXUS Express Stent was minimal
`based on the types and quantities of starting materials (including any
`manufacturing additives).
`
`Long term biocompatibility of the drug/polymer coating on the stent in
`humans is unknown.
`
`B.
`
`In Vivo Pharmacokinetics
`
`81. TAXUS Express2 Paclitaxei-Eiuting Coronary Stent
`
`In the clinical studies, TAXUS I, II, and Ill, no paclitaxellevels were
`detected after stent implantation using an analytical method with a
`lower limit of quantitation (LLOQ) of 10 ng/ml. These findings were
`confirmed in preclinical studies using multiple stents with total
`loaded doses above the clinically available stent system and an
`assay with an LLOQ of 0.03 ng/ml. Hence, in the absence of any
`systemically detectable levels, standard pharmacokinetic
`parameters were not estimated.
`
`82. Drug Interactions
`
`Formal drug interaction studies have not been conducted with the
`TAXUS Express Stent. Paclitaxel is metabolized in the liver via
`cytochrome P450 (CYP) 2C8 to 6-alpha-hydroxypaclitaxel and via
`CYP 3A4 to 3'-p-hydroxypaclitaxel and 6-alpha,3'-p­
`dihydroxypaclitaxel. Paclitaxel is a substrate of P-glycoprotein.
`Because metabolism appears to play an important role in the
`elimination of paclitaxel, agents that could compete with or inhibit
`the CYP2C8 and CYP3A4 isoenzymes may increase paclitaxel
`plasma levels. Potential drug interactions may occur with any drug
`that affects these isoenzymes.
`
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`

`Summary of Safety and Effectiveness Data
`
`TAXUSTM Express2 TM Coronary Stent System (P030025)
`
`C.
`
`In Vitro Engineering Testing
`
`In vitro engineering testing, in accordance with the FDA "Guidance for the
`Submission of Research and Marketing Applications for lnterventional
`Cardiology Devices: Intravascular Stents", May 1995, was conducted on
`the uncoated, bare versions of the Express stent mounted on either the
`Express or Express2 MR and/or OTW delivery catheters, which were
`approved in P020009.
`
`Supplementary in vitro engineering tests were also performed on the
`TAXUS Express Stent mounted on the Express and/or Express2 delivery
`catheters. Some testing was not repeated since there was no change to
`the stent substrate, and where the effect of the coating and minor
`changes in design of the catheter delivery system were assumed to be
`negligible when evaluated against measurement and manufacturing
`tolerances. In tests that were repeated, values for the TAXUS Express
`stent were compared back to the uncoated stent as well as other bare
`metal coronary stents. Values reported for the products tested indicated
`statistical equivalence.
`
`Additional tests were conducted to support the integrity of the coating on
`the TAXUS Express Stent and are summarized separately in Section VIII
`D- Coating Characterization Testing.
`
`The in vitro engineering studies conducted are summarized in Table 4.
`"Pass" denotes that the test results met product specifications and/or the
`recommendations in the above-referenced guidance document.
`
`Pass
`
`Pass
`
`Table 4: Stent and Delivery Catheter Engineerina Testina
`I Conclusion
`Description of Test
`Test
`Stent Material Specification Conformance Testin!l
`Bare Stent Material
`Chemical analysis was conducted on the stainless steel ingot
`provided by the material supplier to confirm both chemical
`Analysis
`analysis and inclusion/impurity content as provided by ASTM
`F138.QO ~standard Specification for Wrought 18 Chromium­
`14 Nickel-2.5 Molybdenum Stainless Steel Bar and Wire for
`Suraicallmolants(UNS S31673l."
`Surface Contamination The fully processed (but not sterilized) TAXUS Express
`stents were examined via SEM at 500X and 2000X to detect
`evidence of surface contamination or impurities on the stent
`material not removed by cleaning processes. Results of
`SEM evaluation showed no evidence of contamination above
`the soecified limits.
`Tensile strength and elongation testing was performed on
`tubing sizes used to fabricate the stents. The tensile
`strength and elongation met the product soecifications.
`As part of the fatigue testing, TAXUS stents were also tested
`according to ASTM F2129-01 "Standard Test Method for
`Conducting Cyclic Potentiodynamic Measurements to
`Determine the Corrosion Susceptibility of Small Implant
`DevicesM to demonstrate that the finished stents exhibit
`corrosion and reoassivation characteristics comoarable to or
`
`Mechanical Properties:
`Tensile Strength &
`Elongation
`Corrosion Resistance
`
`Pass
`
`Pass
`
`Page 10/37
`
`Page 10
`
`Medtronic Exhibit 1424
`
`

`

`Summary of Safety and Effectiveness Data
`
`
`
`TAXUSTM Express2 TM Coronary Stent System (P030025)
`
`Test
`
`Description of Test
`better than marketed 316L bare metal coronary stents. The
`results indicated that the corrosion resistance met product
`soecifications.
`Stent Integrity Testing
`The metal surface coverage as a function of stent diameter
`Metal to Artery
`was calculated by dividing the total vessel contact metal
`Percentage
`surface area of the stent structure by the surface area of the
`vessel at any given stenUvessel diameter. Metal to artery
`percentage ratios were calculated for all of the stent
`diameters recommended in the product labeling, with the
`highest surface to artery ratio (24.7%) occurring when the
`stent is deployed to the smallest diameter 12.5mm\.
`The length of the stents were measured prior to and after
`expansion to the largest nominal diameter. All stents met
`product specifications.
`
`Length Changes Upon
`Expansion: Stent
`Foreshortening
`
`Stent Expansion
`Uniformity
`
`Stent Recoil
`
`Stent Conformability
`Testing
`
`Compression
`Resistance/Radial
`Hoop Strength
`
`Stent Expansion and
`Safety Margin
`
`Magnetic Resonance
`Imaging
`
`Stent Dimensional
`Verification
`
`Testing was conducted to determine the uniformity of stent
`expansion along the stent length. Units were inflated to
`nominal diameters, deflated, and diameter measurements
`were taken at 3 points along the stent length. Measurements
`were averaged and compared to baseline measurements.
`All stents met the uniformity expansion sPecification.
`Testing was conducted to quantify the amount of elastic
`recoil for the stent and correlate this parameter to the
`recommended sizing procedures. The system was inflated
`to nominal diameter and measurements were taken of the
`stent diameter at 3 locations along the stent. The system
`was then deflated and the same measurements taken.
`Results indicated that oroduct soecifications were met.
`Testing was conducted to determine the conformability (axial
`flexibility) of the stent in its expanded state by determining
`the pure bending moment of the stent. All diameter stents
`met specification.
`Testing was conducted to determine the radial resistance of
`the stent to external compression. All stents were expanded
`to nominal stent diameter, placed in a compression tester,
`forces were applied to compress the stent 0.5mm radially,
`and the forces were recorded. All stents met the
`compression resistance specifications.
`Testing was conducted to determine whether the deformation
`experienced by the stent undergoing expansion above the
`maximum rated diameter gives rise to stentor coating
`fractures. No stents exhibited any strut fractures or
`indications of coating integrity issues when visually examined
`at 32X followina overexoansion.
`Bench testing at field strengths of 3 Tesla (T) or less, and a
`maximum spatial gradient of 325 gauss/em, showed that the
`stent should not migrate in this MR environment. This stent
`has not been evaluated to determine if it is safe in MRI
`systems with field strength greater than 3 T.
`
`The following statement is also included in the instructions
`
`for use: 'This product has not been evaluated for heating in
`
`the MR environment. The effect of heating in the MR
`
`environment for overlapping stents or stents with fractured
`
`struts, or on the drug or polymer coating is not known.
`
`MR imaging quality may be compromised if the area of
`
`interest is in the exact same area or relatively dose to the
`
`position of the stent.~
`
`Testing was conducted to measure and optically inspect the
`stent to document that stent dimensional product
`specifications do not deviate from product specifications. All
`
`Page 11/37
`
`Conclusion
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`1'1
`
`Page 11
`
`Medtronic Exhibit 1424
`
`

`

`Summary of Safety and Effectiveness Data
`
`TAXUSTM Express2TM Coronary Stent System (P030025)
`
`Test
`
`Finite Element
`Analysis
`
`10 Year Accelerated
`Pulsatile Fatigue
`Testing
`
`Stent Radiopacity
`
`Description of Test
`product met soecifications.
`An in-depth analysis of the stent was conducted to ensure
`that the implant conditions to which the stent will be
`subjected would not result in failure due to fatigue. The FEA
`evaluated the structural integrity of the stent and coating
`when subjected to the expected loading conditions
`generated in coronary arteries. The analysis took into
`account manufacturing, delivery, implantation and clinical
`loading over the implant life, and predicted that fatigue
`failures will not occur over the 400 million cvcles of loadina.
`Accelerated In vitro testing of approximately 10 years (400
`million cycles) equivalent real time was conducted to ensure
`that the stent, when expanded to its largest intended
`diameters, will not show fatigue failure during simulated 10
`year life span testing. The stents were dynamically cycled
`over simulated vessel conditions for 400 million cycles.
`Following cycling, stents were visually inspected using 40X
`optical microscopy. No signs of strut cracking or breaking
`were detected. Additionally, eight stents (4 coated, and 4
`with coating removed after fatigue testing) were randomly
`analyzed using SEM. All tested stents were free from
`fatigue induced surface defects, and there was no evidence
`of coating fatigue or corrosion. The stent met the 10 year
`accelerated fatigue resistance requirement of the product
`specification.
`Testing was conducted on the bare metal stent as the
`addition of the coating did not add or detract from the
`radiopacity of the stent in clinical use.
`Stent/Catheter Deliverv Svstem TestinQ
`Stents systems with sizes representative of the available
`Balloon in Stent Burst,
`product were tested to burst, and all other sizes were also
`Balloon Bonds, and
`tested and required to meet rated burst pressure. All stent
`Inflation Lumen
`systems met rated burst pressure. The results demonstrate
`Integrity Testing
`with 95% confidence that at least 99.9% of the balloons will
`not experience loss of integrity at or below the rated burst
`pressure.
`Testing was performed to determine how the diameter of a
`deployed balloon varies with applied balloon pressures. The
`stent sizing results verify that the stent systems meet the
`labeled compliance values.
`Testing was performed to determine the TAXUS Express
`and Express stent deployment pressures. Samples of
`every T AXUS Express stent and delivery system and
`representative sizes of the TAXUS Express2 stent and
`delivery system were tested and demonstrated that these
`product met the labeled deployment specification of.=:. 9 atm
`(132 DSi).
`Express2 delivery systems across the range of balloon
`lengths and diameters were tested for inflation/deflation
`times, and all stent svstems met soecifications.
`TAXUS Express" stent systems across the range of
`stenUballoon lengths and diameters were required to
`complete 20 pressurization cycles to Rated Burst Pressure
`(RBP). The stenUballoon burst results show statistically that,
`with 95% confidence, 90% of the catheters will not
`experience balloon, shaft, or proximal/distal seal loss of
`integrity at or below the maximum recommended rated
`balloon burst oressure.
`Stent systems for each diameter balloon were tested to
`determine the deflated stenUballoon profile. All samples met
`the product specification.
`
`Conclusion
`
`n/a
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Page 12/37
`
`ZP
`
`Stent Diameter vs.
`Balloon Inflation
`Pressure (Compliance)
`
`Stent Deployment
`Testing
`
`Balloon Inflation and
`Deflation Testing
`
`Repeat Balloon
`Inflation
`
`StenUBalloon Crossing
`Profile
`
`Page 12
`
`Medtronic Exhibit 1424
`
`

`

`Summary of Safety and Effectiveness Data
`
`TAXUSTM Express2TM Coronary Stent System (P030025)
`
`Test
`Pre- and Post-
`Deployment Catheter
`Withdrawal Forces
`(into a Guide Catheter)
`
`Non-Coaxial
`Withdrawal Forces
`(into a Guide Catheter)
`
`Stent Securement-
`Force Testing
`
`System Track Testing
`
`Full Unit Tensile
`Testing
`
`Description of Test
`Testing was carried out to verify that the TAXUS Express"
`Stent system can be safely withdrawn back into the
`recommended guide catheter sizes both before and after
`stent deployment. This testing also verified that after stent
`deployment, the balloon could be withdrawn from the stent
`Testing indicated that all samples could be withdrawn back
`into the recommended guide catheter prior to and after stent
`delivery. All samples met the product soecification.
`Testing was carried out to demonstrate that the TAXUS
`Express2 stent system can be safely withdrawn into the
`guide catheter when the entry is non-coaxial. Testing
`indicated that all samples could be withdrawn back into the
`recommended guide catheter after tracking through a
`simulated tortuous model. All samples met the product
`specification.
`Testing was conducted to assess the force required to
`displace a crimped TAXUS stent from the Express2 delivery
`systems (1) directly from the balloon catheter, and (2) after
`tracking through a simulated tortuous artery model. All stent
`systems met the stent securement specification. Stent
`securement to the specification was demonstrated with 95%
`confidence that 99.7% of the TAXUS Express stents will not
`be dislodged from the Express2 delivery systems.
`Testing was conducted to demonstrate that the tracking
`force of the TAXUS Exress2 Coronary Stent System through
`a simulated artery is comparable to the Express Coronary
`Stent System. Peak force was measured as the catheter
`was tracked through a simulated artery, and found to be
`comoarable. All sa moles met oroduct specification.
`Representative sizes of the TAXUS Express" stent delivery
`system were tested to determine the tensile strength of the
`delivery catheter. A